Cytotoxic synergism of Clostridioides difficile toxin B with proinflammatory cytokines in subjects with inflammatory bowel diseases

Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating and developing.While in healthy subjects colonization by C.difficile becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C.difficile infection and its progression and relapses.TcdB is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled family.Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only necrosis.It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis.Therefore,in subjects with IBD there are the conditions:(1)For greater susceptibility to C.difficile infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis.The only therapeutic approach currently possible in IBD patients is monitoring of C.difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins.The future perspective is to generate bacteriophages against C.difficile for targeted therapy.

Hepatitis B virus infection, diabetes mellitus, and their synergism for cholangiocarcinoma development: A casecontrol study in Korea

AIM: To identify possible risk factors and their synergism for cholangiocarcinoma development.METHODS: A hospital-based, case-control study in which we included 276 cholangiocarcinoma patients [193 extrahepatic cholangiocarcinoma(ECC) and 83 intrahepatic cholangiocarcinoma(ICC)], diagnosed at a training hospital in Korea between 2007 and 2013, and 552 healthy controls matched 2:1 for age, sex, and date of diagnosis. Risk factors for cholangiocarcinoma and possible synergism between those factors were evaluated using conditional logistic regression and synergism index, respectively.RESULTS:There was an association between cholangiocarcinoma and hepatitis B virus(HBV) infection, diabetes mellitus(DM), cholecystolithiasis, choledocholithiasis, and hepatolithiasis, with the adjusted odds ratios(AORs) of 4.1, 2.6, 1.7, 12.4, and 39.9, respectively. Synergistic interaction on the additive model was investigated between HBV infection and DM(AOR = 12.2; 95%CI: 1.9-80.1). In the subgroup analyses, cholecystolithiasis, choledocholithiasis, hepatolithiasis, and DM were significant risk factors for ECC(AOR = 2.0, 18.1, 14.9, and 2.0, respectively), whereas choledocholithiasis, hepatolithiasis, HBV infection, and DM were risk factors for ICC(AOR = 8.6, 157.4, 5.3 and 4.9, respectively). Synergistic interaction was also observed between HBV infection and DM(OR = 22.7; 95%CI: 2.4-214.1). However, there was no synergistic interaction between other significant risk factors for cholangiocarcinoma.CONCLUSION: In this Korean study, HBV infection and DM were found to exert independent and synergistic effects on the risk for cholangiocarcinoma, including ICC. Exploring the underlying mechanismsfor such synergy may lead to the development of cholangiocarcinoma prevention strategies in high-risk individuals.

Corrosion Inhibition Synergism between Lanthanum(Ⅲ) Ion and 8-Hydroxyquinoline for Zinc in Hydrochloric Acid

The effects of La 3+ ion and chelate reagent 8 hydroxyquinoline on the corrosion rate of zinc in hydrochloric acid were investigated by using weight loss method and electrochemical method. It is found that in a specific concentration range of La 3+ ion and 8 hydroxyquinoline, the obvious corrosion inhibition synergism is obtained. The mechanism of corrosion inhibition synergism was discussed on basis of adsorption theory.

Risk Assessment of Synergism and Recombination on the Transgenic Plants Containing Viral Movement Protein and Replicase Genes

The transgenic tobacco plants transformed with movement protein gene of Tomato mosaic virus (ToMV) or Tobacco mosaic virus (TMV) and partial replicase gene of Cucumber mosaic virus (CMV) P1 isolate (CMV-P1), were inoculated with Potato virus X, Potato virus Y, TMV and CMV isolate RB (CMV-RB), respectively. Symptom observation showed there were no symptom differences in transgenic tobacco plants as compared with those in non-transgenie tobacco plants. ELISA also illustrated that the virus concentrations in the transgenic plants were similar to those in non-transgenic plants, indicating that no synergism is found in these plants. The transgenic tobacco plants expressing movement protein gene of ToMV or partial replicase gene of CMV-P1 were inoculated with TMV and CMV-RB, respectively. The local or systemic infected leaves were then used for elucidation of the possible virus recombination in transgenic plants with biological infectivity test, ELISA and immuno-capture RT-PCR. Within 16 months, no recombination was found between transformed genes and inoculated virus genomes. The research provides fundamental data for understanding of the possible risk of the transgenic plants expressing viral sequences.

Anti-listerial synergism of leaf essential oil of Metasequoia glyptostroboides with nisin in whole,low and skim milks

Objective:To examine the individual and synergistic anti-listcrial effect of nisin and leaf essential oil of Metasequoia glyptostroboides(M.glyptostroboides) against one of the leading foodhorne pathogens Listeria monocytogenes(L.monocytogenes) ATCC 19116 in milk samples.Methods:The whole(8%),low(1%) and skim(no fat content) milk samples were inoculated with L.monocytogenes ATCC 19116 along with leaf essential oil of M.glyptostroboides or nisin alone as well in eomhinations.Results:In this study,the leaf essential oil at the concentrations of 2% and 5% revealed strong anti-listerial effect against L.monocytogenes ATCC 19116 in all categories of milk samples.Nisin at the concentrations of 250 and 500 IU/mL displayed a strong inhibitory effect against ATCC 19116 as compared to the control group.Additionally,synergistic combinations of leaf essential oil(1%) and nisin(62.5,125.250 and 500 IU/mL) also had a remarkable anti-listerial synergism in all the tested milk samples including whole,low and skim milk after 14 days.Conclusions:As a major finding,the leaf essential oil of M.glyptostroboides might he a useful candidate for using in food industry to control the growth of foodhorne pathogenic bacteria as confirmed by its potent anti-listerial Synergistic effect with nisin against L.monocytogenes ATCC 19116 in different milk samples.

SYNERGISM OF WOLFRAMITE FLOTATION WITH BENZYL ARSONIC ACID AND SODIUM BUTYL XANTHATE

Wolframite notation with benzyl arsonic acid and sodium butyl xanthate is studied,at first.It shows the efficiency of mineral processig is good when the two agents are added together.Then the synergism of sodium butyl xanthate and benzyl arsonic acid is studied also by HPLC.

Ceruloplasmin or Fibronectin Synergism with Quartz Dust on Stimulating Collagen Gene Transcription in Human 2BS Fibroblast

Human α1(Ⅰ), α2(Ⅰ) and α1(Ⅲ) cDNA probes and RNA dot hybridization were employed to quantitate collagen mRNA changes after adding silica dust into the media of human 2BS fibroblasts. At all dosages used (100, 200, 500 and 1000μg), the α1(Ⅰ), α2(Ⅰ)and α1(Ⅲ) mRNA levels increased one day after dusting. At the same dosage of silica (100μg), α1(Ⅲ) mRNA increased earlier than type Ⅰ collagen mRNA did. The type Ⅰ and type Ⅲ collagen mRNA contents in the experimental groups were higher than those in control on days 3, 5, 7 and 9. The effect of ceruloplasmin (Cp) and fibronectin (Fn) on collagen mRNA synthesis was also studied, after adding silica dust, Cp or Fn into the media of human 2BS fibroblast. The results showed that Cp and Fn have stimulating effect on collagen mRNA production. When both Cp and silica dust were added into cell culture media, the collagen mRNA level was increased more than those of adding either Cp or silica dust alone. Similar situations were found for Fn. Cp (or Fn) synergism with silica dust on stimulating transcription of human collagen gene was suggested

Effects of Synergism Between PVY and PVX on Virus Titer and Cell Ultrastructure in Tobacco Plants

The viruses titer and the ultrastructure of infected cells in tobacco host (Nicotiana tabacum cv. Samsun), which doubly infected with potato virus Y necrosis strain (PVYN) and potato virus X (PVX), were studied under greenhouse conditions. The results indicated that PVYN and PVX interacted synergistically. and tobacco plants which doubly infected with PVX and PVYN could greatly increase symptom severity as compared with that induced by the single virus. As determined by triple antibody sandwich enzyme-linked immunosor-bent assay (TAS-ELISA), the titer of PVX in the tobacco leaves infected with both PVYN and PVX was up to 9.10 times higher than the plants infected with PVX only. No significant differences in PVYN titer were detected between singly and doubly infected plants. The enhancement of PVX titer in doubly infected plants was evident in greenhouse and was independent of the virus strains, tested seasons, intervals between PVYN and PVX inoculation. When sections of doubly infected leaves were examined with an electron microscope, it could be frequently found that cells contained pinwheels and large masses of PVX-like particles, pinwheels and laminate inclusions, or all three structures, most of them were swollen, and their chloroplast and other organella were destructed heavily. This suggested that doubly infected cells were involved in the enhancement phenomenon, which seemed to be the result of an increase in the amount of PVX synthesized in them.

Synergism of Plasma and Catalyst on the Dehydrogenative Coupling of Methane

At atmospheric pressure and ambient temperature, pulse corona induced plasma was used as a new method for dehydrogenative coupling of methane. The synergism of plasma and catalyst on dehydrogenative coupling of methane was investigated. Experimental results have revealed that the synergism does exist, when positive corona within a suitable power range and an intermediate pulse repetition frequency (PRF) for a loaded 7-Mn2O3/7-A12O3 catalyst were chosen. In respect to the mechanism approach, a tentative model for general pathway was proposed to explain the role of plasma and catalyst partaking in the process of methane decomposition and C2 products formation.

In vitro assessment of the synergism between extracts of Cocos nucifera husk and some standard antibiotics

Objective: To evaluate the interactions between the crude extracts of Cocos nucifera(C.nucifera) and six front line antibiotics(ampicillin sodium salt, penicillin G sodium,amoxicillin, chloramphenicol, ciprofloxacin and tetracycline hydrochloride), against some bacterial pathogens linked with human infection.Methods: The pulverized husk of C.nucifera was dissolved in 95% n-hexane and extracted using Soxhlet extraction method and sterile distilled water(aqueous).The antibacterial susceptibility of the crude extracts of C.nucifera was tested against environmental and clinical strains(6) obtained from the South African Bureau of Standards(SABS), Vibrio(6) and Listeria pathogens(6).The agar-well diffusion method was used for screening the extracts for their antibacterial activity.The minimum inhibitory concentration and minimum bactericidal concentration of the extracts were determined.Time-kill assay was used to evaluate bactericidal and/or bacteriostatic activity.The synergistic effect of the crude extracts and antibiotics was assessed and evaluated by adopting the checkerboard methods.Results: With the time-kill assay, the highest bactericidal activity was observed on Vibrio fluvialis EL041 with a-5.6 ± 0.2 log_(10)CFU/mL decrease in cell density as a result of the combination of the extracts and chloramphenicol at two-fold minimum inhibitory concentrations.Synergisms using the time-kill assay constituted about 72%, while indifference constituted about 28%.The checkerboard method revealed synergistic interaction in 67% of the combinations, and indifference in 33%.There was no specificity in the observed synergy to a particular class of antibiotics.Conclusions: This investigation suggests the crude extracts of C.nucifera to be a potential broad spectrum antimicrobial compound.Therefore, further study is needed to isolate the pure compounds from these crude extracts.

No synergism between bis(propyl)-cognitin and rasagiline on protecting dopaminergic neurons in Parkinson's disease mice

Rasagiline,a monoamine oxidase-B inhibitor,and bis（propyl）-cognitin（B3C）,a novel dimer are reported to be neuroprotective.Herein,the synergistical neuroprotection produced by rasagiline and B3 C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）-induced mice of Parkinsonism.By using neurobehavioural tests,high-performance liquid chromatography and western blot assay,we showed that B3 C at 0.3 mg/kg,rasagiline at 0.02 mg/kg,as well as co-treatment with B3 C and rasagiline prevented MPTP-induced behavioural abnormities,increased the concentrations of dopamine and its metabolites in the striatum,and up-regulated the expression of tyrosine hydroxylase in the substantia nigra.However,the neuroprotective effects of co-treatment were not significantly improved when compared with those of B3 C or rasagiline alone.Collectively,we have demonstrated that B3 C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects.

Effect of Mitigating Strength Retrogradation of Alkali Accelerator by the Synergism of Sodium Sulfate and Waste Glass Powder

This work aims to utilize waste glass powder(WGP)as a plementary material to mitigate the strength shrinkage caused by the alkaline accelerator.Waste glass power was used to replace cement by 0%,10%,and 20%to evaluate waste glass powder on the alkaline accelerator’s strength retrogradation.The results show that the strength improvement effect of unitary glass powder is inconspicuous.Innovative methods have been proposed to use sodium sulfate and waste glass powder synergism,using the activity of amorphous silica in glass powder.Compared with the reference group,the compressive strength of 28d mortar increases by 67%when the sodium sulfate content is 2.5%,and the replacement amount of waste glass powder is 10%.Besides,XRD and SEM analysis of hydration products also confirmed that the synergistic effect of sodium sulfate and waste glass powder could reduce strength inversion.The findings presented in this paper are pivotal for using waste glass to solve the problem of strength inversion caused by the alkaline accelerator.

Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles

Immunotherapy has revolutionized the landscape of cancer treatment.However,single immunotherapy only works well in a small subset of patients.Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome.Nevertheless,the synergistic,additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored.Herein,we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4(PAK4)silencing with immunogenic phototherapy in engineered extracellular vesicles(EVs)that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with si RNA against PAK4 and a photoactivatable polyethyleneimine.The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy,thus contributing to effective antitumor effects in vitro and in vivo.Moreover,the antitumor synergism of the combined treatment was quantitatively determined by the Compu Syn method.The combination index(CI)and isobologram results confirmed that there was an antitumor synergism for the combined treatment.Furthermore,the dose reduction index(DRI)showed favorable dose reduction,revealing lower toxicity and higher biocompatibility of the engineered EVs.Collectively,the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs,which is promising for boosting the therapeutic outcome of cancer immunotherapy.

Synergism and anion-cation dual chemical substitution in heterostructure sprouted on MXene enable high-efficiency and stable overall water splitting

The exploration of novel,super-potent and low-cost electrocatalysts for water splitting has always been the kernel in the field of renewable sources.Herein,exfoliated Ti_(3)C_(2)T_(x) MXenes work as a substrate to vertically grow polypore N,Ni-Co2P nanoarrays(N,Ni-Co2P@TC)through an in situ interface-growth strategy and subsequent phosphorization and nitridation.The well-defined heterointerfaces with positive and negative ions co-modulation as coupled hydrogen evolution reaction(HER)and oxygen evolution reaction(OER)catalysts for efficient overall water splitting are investigated,which possesses excellent durability even at a large current density(±500 mA cm^(-2)).For HER,suitable H_(2)O∗and H∗absorption energies and accelerated electronic transmission make N,Ni-Co2P@TC display a low overpotential of 27 mV at-10 mA cm^(-2) and Tafel slope of 38 mV dec^(–1) in 1 mol/L KOH.For OER,the synergy of N,Ni-Co2P@TC with selfreconfiguration can give enhanced activity with a low overpotential of 232 mV at 10 mA cm^(-2) and a Tafel slope of 57 mV dec^(–1).Additionally,the excellent bifunctional activity allows easily combining for efficient overall water splitting with a low driving voltage(1.51 V)at 10 mA cm^(-2),and the electrolyzer can be driven by a 1.5 V AAA battery.

A Rapid Parameter of Enzyme-Treated Cellulosic Material Revealed by Reducing Sugar Release

This study was conducted to evaluate the effectiveness of enzymes in purifying and reducing the degree of polymerization of cellulose for the production of dissolving pulp.Our goal was to determine the contributions of xylanase(X)and endoglucanase(EG)in the treatment of pulp,specifically by quantifying the formation of soluble and insoluble reducing sugars using the dinitrosalycilic acid(DNS)test.Predominantly,the release of soluble reducing sugars(RSSol)was enhanced after xylanase treatment,while endoglucanase(EG)treatment led to changes in insoluble reducing sugars(RSIns).The maximum synergism was observed for RSIns when a high ratio of endoglucanase to xylanase(320EG:5X/g pulp)was used.The relative contribution of endoglucanase to RSins was determined to be 15.6%of the total reducing sugar.The viscosity of pulps treated with xylanase decreased only by 7%,whereas endoglucanase treatment significantly reduced viscosity by 45%.Modifications in the particle size were observed after pulp treatment with the combination of endoglucanase and xylanase.In summary,the DNS test is a rapid and effective method for evaluating the efficiency of enzyme treatments on pulps.The measurement of RSIns correlates with changes in pulp viscosity to different extents,providing valuable insights into the effectiveness of enzyme treatments.

Synergistic interactions of catalpol and stachyose in STZ-HFD induced diabetic mice: Synergism in regulation of blood glucose, lipids, and hepatic and renal function

Objective: Rehmanniae Radix has been traditionally used to treat diabetes. Catalpol(CAT) and stachyose(STA) are two of the main bioactive compounds in Rehmannia Radix and found to have similar therapeutic effects on diabetes and its complications. In this paper, we aimed to investigate whether there were synergistic therapeutic effects of CAT and STA on diabetes.Methods: Streptozotocin(STZ) with the feeding of high-sugar-high-fat diet(HFD) was applied to induce diabetic C57BL/6 mice. STZ-HFD induced diabetic mice were then divided into model and six medicaltreated groups: metformin(MET), STA, CAT, and three combinations of CAT:STA(1:1, 1:2, 2:1). Blood, liver,and kidney samples were isolated after six-week oral administration for biochemical assays of serum lipids, the indicators of kidney and liver functions and HE staining for liver tissues.Results: It turned out that CAT, STA and their three combinations(1:1, 1:2, 2:1) could effectively control body weight, blood glucose, kidney weight and liver weight index, and well regulate levels of TC, HDL-c,TG, ALT, and TBA. In addition, CAT and its combination with STA at the ratio of 2:1 could significantly improve albumin content, compared to that in model group. STA and CAT and their combinations showed the improvements on kidney function in terms of urinary creatinine(Ucr). However, there were no such consistent observations on serum creatinine(Scr) and creatinine clearance rate(Ccr). The combination of CAT and STA at the ratio of 1:1 exhibited the better adjusting effects on kidney weight and liver weight indexes and the levels of ALT, Ucr, Scr, and Ccr. Our results demonstrated that the combinations of CAT and STA especially 1:1 showed similar or better improvements on diabetes-associated complications,compared to the sole CAT or STA treatment.Conclusion: Thus, we concluded that there were synergistic therapeutic effects between CAT and STA on STZ/HFD-induced type 2 diabetes. This project provided insights and technical supports for the innovation of discovering bioactive constituents in Rehmannia Radix and studying its integrative mechanism in curing diabetes.

Enhanced removal of organic pollutant by separable and recyclable rGH-PANI/BiOI photocatalyst via the synergism of adsorption and photocatalytic degradation under visible light

A novel three-dimension separable and recyclable r GH-PANI/BiOI photocatalyst with the synergism of adsorption-enrichment and photocatalytic-degradation was successfully prepared via a facile three-step hydrothermal method.The three-dimension reduced graphene oxide hydrogel(rGH)in with flower-like BiOI photocatalyst uniformly distributed not only possesses excellent adsorption and electron transport properties,but also is easy to be separated from water for recycling.In addition,polyphenylamine(PANI)provides superior hole transport ability due to its delocalizedл-лconjugate structure.The cooperation of rGH and PANI greatly enhances the separation efficiency of photogenerated carriers,and finally improves the photocatalytic degradation behaviors.The removal rates of Rhodamine B(RhB)by rGH-PANI/BiOI-70%composite under visible light respectively reach 100%and 50.13%in static and dynamic systems,which are 12.85 and 3.58 times of BiOI,respectively.The removal rate does not show decrease after 5 recycles indicating the excellent separable and recyclable property of rGH-PANI/BiOI photocatalyst.The work provides an essential reference for designing and constructing hydrogel-based ternary composite photocatalysts with excellent synergism of adsorption and photocatalysis,which shows great potential in the treatment of water pollution.

Formation and Characteristics of Middle-phase Microemulsions——Effect of Synergism of Surfactants, Alcohol and Oil

Microemulsions can be divided into simple-phase microemulsions and multi-phasemicroemulsions. The former is a system with only an independent phase while the lat-ter corresponds to a multi-phase system comprising the microemulsions and another(oil or water) or two (oil and water) phases. When the microemulsions are in the mid-

Compatibilization-crosslinking synergism in PVC/PE blend

It has been reported that compatibilizer or crosslinking agent can improve the compatibilization of PVC/PE blends. And we have found that the mechanical properties of poly(vinyl chloride) (PVC)/low density polyethylene (LDPE) blends were dramatically improved by compatibilization together with crosslinking. According to these,the compatibilization-crosslinking synergism was proposed. This letter reports the influ-

Compatibility mechanism of Chinese medicine formula:state of the art and perspectives

Traditional Chinese medicine(TCM)has been practiced in China and surrounding countries for thousands of years and has gradually attracted the attention of Western countries.After reasonable compatibility,TCMs could play the key role of enhancing efficacy and reducing toxicity,which has significant therapeutic advantages in the treatment of complex diseases in clinical practice.While the TCM compatibility is not the simple addition of drugs.Under the appropriate dosage ratio,multiple TCMs can play a synergistic role to realize the overall regulation of TCM treatment.Therefore,it is of critical essential to study the compatibility of TCM formula to promote TCM modernization,new drug development and clinical application.Recently,under the guidance of TCM theory,many researches on the composition,pharmacodynamic activity and pharmacokinetic properties of TCM formula have emerged by integrating new technologies and new methods,revealing the scientific connotation of the compatibility of TCM formula from different perspectives and levels.This paper introduces the research progress of compatibility rules from different levels of compatibility,compatibility for synergistic enhancement and detoxification,and application of cutting-edge technology,with representative cases,in order to provide ideas and references for further study on TCM compatibility.